It has been suggested that in embryogenesis hair follicles are formed by reciprocal interactions between the epidermis and underlying mesoderm [1,2,3,4]. Dermal Papillae (DP) first arise as cell condensates in the dermis in response to epidermal placode formation. As hair follicles progress in development, epidermal cells in placodes proliferate actively and envelope the dermal condensates, now called dermal papillae, separating them from surrounding dermis [5]. Exposed to these new niche conditions, DP cells acquire the expression of BMP-4, its inhibitor noggin, and the surface markers N-CAM and p-75. Additionally, they secrete specific extracellular matrix proteins (e.g. versican (VCAN)) and show high level of alkaline phosphatase activity (AP) [6]. Using double reporter Lef1-RFP/K14-H2BGFP mice, studies have identified detailed genetic signature of prospectively isolated mouse DP cells [7] and identified Wnt, BMP and FGF singling pathway as a requirement for murine DP maintenance and function [8,9,10]. DP cells play a role in hair growth and cycling [6] and determine hair size and hair type [11,12]. It has been long recognized that DP cells are able to induce hair follicle formation not only in embryogenesis but also postnatal. Vibrissae DP cells induced de novo hair formation when transplanted into the footpad of the adult rat, which is normally a non-haired skin area [13]. Human DP cells isolated from scalp skin contribute to hair formation when transplanted into rodents [14,15] and induce keratinocytes morphogenesis in cultures [16].
DP cells have been proposed as a cell-based treatment for hair loss diseases. However, human DP cells are not suitable for this purpose because they cannot be obtained in necessary amounts and rapidly lose their ability to induce hair follicle formation when cultured [7,8,17,18]. Therefore, there is an unmet need to develop functional DP cells capable of inducing a robust hair growth.